Insular cortex neurons encode and retrieve specific immune responses

Tamar Koren, Re'ee Yifa, Mariam Amer, Maria Krot, Nadia Boshnak, Tamar L. Ben-Shaanan, Hilla Azulay-Debby, Itay Zalayat, Eden Avishai, Haitham Hajjo, Maya Schiller, Hedva Haykin, Ben Korin, Dorit Farfara, Fahed Hakim, Oren Kobiler, Kobi Rosenblum, Asya Rolls

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain's insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.

Original languageEnglish
Pages (from-to)5902-5915.e17
JournalCell
Volume184
Issue number24
DOIs
StatePublished - 24 Nov 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

Funding

This work was supported by the ERC STG, NIEMO ( 758952 ) and the Prince Center for Neurodegenerative Disorders of the Brain . A.R. is a Howard Hughes Medical Institute (HHMI)-Wellcome Trust international scholar. We would like to thank J. Gross, D. Khatib, D. Derdikman, Y. Berger, and O. Barak for helpful discussions and technical support; S. Schwarzbaum for editing the manuscript and her insightful comments; A. Grau, A. Shemesh, O. Shenker, E. Suss-Toby, S. Huleihel, N. Dahan, and Y. Sakoury for technical support; and M. Schlesinger, T. Hass, R. Shofti, and the preclinical research facility team for their help with the rodent work. This work was supported by the ERC STG, NIEMO (758952) and the Prince Center for Neurodegenerative Disorders of the Brain. A.R. is a Howard Hughes Medical Institute (HHMI)-Wellcome Trust international scholar. T.K. designed and carried out all the experiments, interpreted the results, and wrote the manuscript. R.Y. M.A. M.K. N.B. H.D. and E.A. contributed to the experimental design, execution, and data analysis. T.L.B.-S. contributed to the development of the experimental design. I.Z. H. Hajjo, M.S. B.K. H. Haykin, and D.F. contributed to the execution of the experiments. O.K. contributed to the anatomical tracing. F.H. and K.R. contributed to the experimental design and the interpretation of the results. A.R. contributed to the experimental design and data interpretation and wrote the manuscript. All authors commented on the final manuscript. A.R. T.K. T.L.B.-S. and H.A.-D. have a patent application related to this work.

FundersFunder number
NIEMO758952
Prince Center for Neurodegenerative Disorders
Howard Hughes Medical Institute
Wellcome Trust
European Research Council

    Keywords

    • engram
    • inflammation
    • insular cortex
    • memory
    • neurons
    • psychosomatic

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